Two novel SNPs Rs1736952 and Rs17354984 are highly associated with uveitis in ankylosing spondylitis.

Abstract

Background: Noninfectious anterior uveitis shares genetic factors, including HLA-B27, with ankylosing spondylitis (AS). The aim of this study was to identify significant single nucleotide polymorphisms (SNPs) associated with noninfectious anterior uveitis in AS patients, which could help predict the risk of developing this condition and provide deeper insights into its genetic underpinnings.

Methods: A genome-wide association study (GWAS) was conducted utilizing the genomic data of 468 AS patients, including 90 with noninfectious anterior uveitis and 378 without it, from the Taiwan Precision Medicine Initiative. This study identified associated genes via SnpXplorer and developed a polygenic risk score (PRS) model to identify AS patients with increased risk of noninfectious anterior uveitis. Biological pathways were analyzed via Enrichr-KG and various databases.

Results: GWAS revealed two novel SNPs, rs1736952 and rs17354984, with p values < 5x10-8, and seventy-four SNPs with p values < 1x10-4. The associated genes were involved mainly in antigen presentation, interferon signaling, immune regulation pathways, ciliary movement, and neurodegeneration. An optimal PRS model was built using nineteen SNPs with an area under the curve of 0.907.

Conclusion: Our results revealed that two novel and significant SNP loci, rs1736952 and rs17354984, are strongly associated with noninfectious anterior uveitis in patients with ankylosing spondylitis. However, their roles in uveitis and other immune disorders warrant further investigation.